bims-mesote 2026-04-19 papers

Issue of 2026–04–19
five papers selected by
Laura Mannarino, Humanitas Research

Front Oncol. 2026 ;16 1778121

From biology to therapy: current standards and emerging strategies in pleural mesothelioma.

J H L T van Genugten, C J de Gooijer, Paul Baas.

Pleural mesothelioma (PM) is an aggressive malignancy with limited therapeutic options and poor long-term prognosis. Platinum-based chemotherapy has been the standard-of-care for most patients for decades. While the decoding of the genomic alterations in PM has triggered renewed interest in mesothelioma biology and targeted therapies, these have yet to reach clinical practice. The recent introduction of dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab has marked the first major advance in PM treatment for decades, yet, many patients do not respond to these drugs and durable long-term responses remain rare. A range of alternative treatment modalities are currently under clinical investigation in PM, including antibody-drug conjugates, bi-specific antibodies, chimeric antigen receptor T-cells, cancer vaccines, and oncolytic viruses. Here we review recent progress in the understanding of PM biology and evaluate relevant phase I-III clinical trials aimed at improving treatment for this disease. We also highlight ongoing and future clinical trials with promising candidates for PM therapy.

Keywords: anti-angiogenic therapy; clinical trials; combination therapy; immune checkpoint blockade; immunotherapy; pleural mesothelioma

DOI: https://doi.org/10.3389/fonc.2026.1778121

Curr Opin Pulm Med. 2026 Apr 15.

Update on pleural mesothelioma.

Deshawn Chong Xuan Tan, Wee Loong Chin, Yun Chor Gary Lee.

PURPOSE OF REVIEW: Pleural mesothelioma remains a universally lethal cancer with a rising global burden. This underscores the need for pulmonologists to stay abreast of evolving diagnostic and therapeutic strategies.
RECENT FINDINGS: This review highlights paradigm shifts in nomenclature, including recognition of mesothelioma in-situ as a pre-invasive entity made possible by molecular markers defining malignant transformation. High impact randomized clinical trials have provided evidence that radical surgical resection, via extrapleural pneumonectomy or extended pleurectomy/decortication, negatively impacts survival and quality of life. Dual immunotherapy (of nivolumab and ipilimumab) is now incorporated as first-line systemic therapy especially for sarcomatoid-containing mesothelioma. Addition of pembrolizumab to standard pemetrexed and platinum chemotherapy provides modest benefits. Emerging approaches are highlighted and encompass molecularly targeted, metabolic, intrapleural, and artificial intelligence (AI)-based strategies.
SUMMARY: These developments underline a move away from aggressive surgical cytoreduction towards more biologically-informed, less invasive management and earlier detection in high-risk cohorts, while embracing biomarker-driven systemic and intrapleural therapies to optimize outcomes. Future research should prioritize mesothelioma-specific trials to define the role and sequencing of perioperative immunotherapy and novel agents. AI tools may assist disease diagnosis, prognostication, and treatment selection.

Keywords: immunotherapy; mesothelioma; mesothelioma in situ; pleural; surgery

DOI: https://doi.org/10.1097/MCP.0000000000001272

Transl Lung Cancer Res. 2026 Mar 23. 15(3): 66

MET amplification in diffuse pleural mesothelioma and response to savolitinib: a case report.

Yueying Chen, Mengyi Shen, Jiawen Lv, Yuwen Rui, Chunwei Xu, Dong Wang, Tangfeng Lv.

Background: Pleural mesothelioma (PM) is a rare malignancy globally, most frequently associated with alterations in tumor suppressor genes such as NF2, BAP1 and CDKN2A. In contrast, mutations or amplifications of the MET gene are seldomly reported in PM.
Case Description: Here, we report the case of a 60-year-old East Asian male without asbestos exposure, never-smoker, diagnosed with advanced PM. The disease proved refractory to multiple lines of therapy, including platinum-based chemotherapy, immunotherapy, intrathoracic instillation and a subsequent individualized regimen comprising intraperitoneal cisplatin plus sintilimab for local disease control and potential immunomodulation synergized with oral anlotinib. Following disease progression accompanied by rapidly accumulating seroperitoneum and pelvic effusion, next-generation sequencing (NGS) of ascitic fluid revealed MET gene amplification, and the subsequent switch to savolitinib controlled the malignant ascites. Unfortunately, the patient died of sudden cardiac and respiratory arrest in December 2023.
Conclusions: This case underscores the critical importance of comprehensive genetic testing in guiding the treatment of advanced PM, particularly after the failure of standard therapies. It illustrates that rare but actionable genomic alterations, such as MET amplification, can be identified through liquid or tissue biopsy and can inform successful targeted treatment strategies, even in a tumor type where such alterations are uncommon. Histological classification combined with molecular profiling remains pivotal for personalized oncology.

Keywords: MET amplification; case report; pleural mesothelioma (PM); savolitinib

DOI: https://doi.org/10.21037/tlcr-2025-aw-1313

J Immunother Cancer. 2026 Apr 15. pii: e014516. [Epub ahead of print]14(4):

Regional immunosuppression and associated systemic markers in focally relapsed sarcomatoid mesothelioma: case report.

Hely Ollila, Prateek Kulkarni, Hyojin Kim, Pratiti Ankola, Navin K Chintala, Carlos Thomas, Jennifer L Sauter, Michael Offin, Prasad S Adusumilli.

A 52-year-old man presented with sarcomatoid diffuse pleural mesothelioma that had relapsed at an isolated site after a complete response to dual-immune checkpoint inhibition (ICI). Targeted sequencing exhibited amplification of chromosome 9p24, encompassing JAK2, PD-L1, PD-L2, and PTPRD in the relapsed (post-ICI) tumor, compared with baseline (pre-ICI). On multiplex immunofluorescence, tumor-associated macrophages (TAMs) and CD8+ cytotoxic T lymphocytes (CTLs) made up most of the cells in baseline and relapsed tumor (59% and 47%, respectively). Baseline tumor cells expressed genes linked to extracellular matrix remodeling and epithelial-mesenchymal transition, intermixed with M2-like TAMs and tissue-resident, effector-like CTLs. Relapsed tumor cells shifted to a growth factor-driven phenotype (NT5E, NOD1, GATA2, FN1, PDCD1LG2) that is known to cause functional impairment of CTLs, which then transitioned to an exhausted state (FCRL3, CST7, GPR171, TRAT1, LAG3); exhausted CD8+ and CD4+ T cells are seen in the peripheral blood at relapse. TAMs were enriched in antigen-presentation (CD80, CD86, CXCL10), extracellular matrix-degradation (MMP9, CTSL), and CTL-suppression (ARG1, PLA2G7) pathways. Our analyses revealed that regional immunosuppression mediated by adaptive reprogramming of tumor-cell and immune-cell (TAMs, CTLs)-intrinsic changes-rather than by immune evasion or stromal exclusion-served as a mechanism of acquired resistance to dual-ICI therapy.

Keywords: Genetic; Immune Checkpoint Inhibitor; Mesothelioma

DOI: https://doi.org/10.1136/jitc-2025-014516

Int Arch Occup Environ Health. 2026 Apr 13. pii: 21. [Epub ahead of print]99(3):

Autopsy reports and asbestos exposure from mesothelioma patients: a population-based study in Northeastern Italy.

Flavia D'Agostin, Corrado Negro, Fabiano Barbiero, Paola De Michieli, Rossana Bussani, Maurizio Pinamonti, Francesca Larese Filon, Francesca Rui.

Keywords: Autopsy findings; Malignant mesothelioma; Occupational asbestos exposure; Pleural plaques

DOI: https://doi.org/10.1007/s00420-026-02207-5